Plasticity of Hippocampal Subfield Volume Cornu Ammonis 2+3 Over the Course of Withdrawal in Patients With Alcohol Dependence

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Abstract

IMPORTANCE

Research focusing on plasticity has shown adult neurogenesis in hippocampal subfields. Chronic alcoholism is associated with decreased plasticity and reduced whole hippocampal volume that could contribute to neuropsychiatric characteristics and outcome of the disease.

OBJECTIVE

To investigate the effect of alcohol abstinence on neuronal plasticity measured as longitudinal volume change in distinct hippocampal subfields.

DESIGN, SETTING, AND PARTICIPANTS

We acquired high-resolution structural images of 42 patients addicted to alcohol and 32 healthy control participants. Patients and control participants were both scanned twice, once after withdrawal and 2 weeks later.

MAIN OUTCOMES AND MEASURES

Volumes of hippocampal subfields cornu ammonis (CA) 2+3, CA4+dentate gyrus, and subiculum were determined with a user-independent segmentation method.

RESULTS

We found plasticity effects in bilateral CA2+3 in patients addicted to alcohol. Compared with healthy control participants, patients had lower CA2+3 volume at pretest (t31 = −0.73, P = .47) and showed a significant normalization of gray matter volume 2 weeks later. Pretest CA2+3 (t31 = −3.93, P < .001) volume was negatively associated with years of regular alcohol consumption (r42 = −0.32, P < .05) and more severe alcohol-withdrawal symptoms (r38 = −0.35, P < .05). Patients with stronger withdrawal symptoms displayed the largest volume increase of CA2+3 (r38 = 0.55, P < .001).

CONCLUSIONS AND RELEVANCE

The observed normalization of the bilateral hippocampal CA2+3 volume deficit matches animal data, showing a strong increase of hippocampal neurogenesis after cessation of alcohol consumption, and fits the reported increase of patients’ cognitive function within a few months of alcohol abstinence. The role of CA3 in pattern separation and completion is also critical for formation of hallucinations, which constitute a severe symptom of the withdrawal syndrome. The study adds further biological arguments from structural brain research to abstain from alcohol.

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